Posttraumatic Stress Disorder Symptoms and Cardiovascular and Brain Health in Women
Authors: Rebecca C. Thurston, Karen Jakubowski, Yuefang Chang, Minjie Wu, Emma Barinas Mitchell, Howard Aizenstein, Karestan C. Koenen, Pauline M. Maki
Journal: JAMA Network Open (2023)

Importance Posttraumatic stress disorder (PTSD), cardiovascular disease (CVD), and Alzheimer disease are major public health issues, particularly for women. The implications of PTSD for cardiovascular and brain health for women is poorly understood. Objective To assess whether PTSD symptoms among midlife women are associated with carotid intima media thickness (IMT), an indicator of carotid atherosclerosis; brain white matter hyperintensity volume (WMHV), an indicator of brain small vessel disease; and cognitive performance and to test a modifying role of the APOE ε4 genotype. Design, Setting, and Participants In this cross-sectional study, participants were enrolled between 2016 to 2021 and completed questionnaires (PTSD Checklist–Civilian Version), physical measures, phlebotomy, neuropsychological testing, a carotid ultrasonographic examination, and 3-Tesla brain magnetic resonance imaging. Participants included community-based women ages 45 to 67 years without a history of CVD, stroke, or dementia. Data were analyzed from July 2022 to September 2023. Exposures PTSD symptoms. Main Outcomes and Measures Outcomes of interest were associations of PTSD symptoms with carotid IMT, brain WMHV, and cognition, assessed in linear regression models. Interactions by APOE ε4 were tested. Covariates included age, race and ethnicity, education, and CVD risk factors. Results Among 274 participants (mean [SD] age, 59.03 [4.34] years; 6 Asian participants [2.2%]; 48 Black participants [17.5%]; 215 White participants [78.5%]; 5 multiracial participants [1.8%]), 64 participants (24.71%) were APOE ε4 genotype carriers. Higher PTSD symptoms were associated with greater carotid IMT (multivariable β = 0.07 [95% CI, 0.01 to 0.13]; P = .03). Associations of PTSD symptoms with neurocognitive outcomes significantly varied by APOE ε4 status. Among women with APOE ε4, PTSD symptoms were associated with greater whole-brain WMHV (β = 0.96 [95% CI, 0.30 to 1.63]; P = .009), periventricular WMHV (β = 0.90 [95% CI, 0.24 to 1.56]; P = .02), deep WMHV (β = 1.21 [95% CI, 0.23 to 2.20]; P = .01), and frontal WMHV (β = 1.25 [95% CI, 0.05 to 2.45]; P = .04), as well as with poorer cognition, specifically attention and working memory (β = −3.37 [95% CI, −6.12 to −0.62]; P = .02), semantic fluency (β = −6.01 [95% CI, −10.70 to −1.31]; P = .01), perceptual speed (β = −12.73 [95% CI, −20.71 to −4.75]; P = .002), and processing speed (β = −11.05 [95% CI, −17.80 to −4.30]; P = .002) in multivariable models. Conclusions and Relevance In this cross-sectional study of midlife women, greater PTSD symptoms were associated with higher carotid atherosclerosis and, among women who were APOE ε4 carriers, greater brain small vessel disease and poorer cognitive performance. These findings point to the adverse implications of PTSD symptoms for cardiovascular and neurocognitive health among women in midlife, particularly for women who are APOE ε4 carriers.